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Updated: Apr 9, 2026
Murine Drinking Models in the Development of Pharmacotherapies for Alcoholism: Drinking in the Dark and Two-bottle Choice
Published on: January 7, 2019
Phosphodiesterase regulation of alcohol drinking in rodents
1Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 North Torrey Pines Road, SP30-2400, La Jolla, CA 92037, USA.
Abstract:
Alcohol use disorders are chronically relapsing conditions characterized by persistent drinking despite the negative impact on one's life. The difficulty of achieving and maintaining sobriety suggests that current treatments fail to fully address the underlying causes of alcohol use disorders. Identifying additional pathways controlling alcohol consumption may uncover novel targets for medication development to improve treatment options. One family of proteins recently implicated in the regulation of alcohol consumption is the cyclic nucleotide phosphodiesterases (PDEs). As an integral component in the regulation of the second messengers cyclic AMP and cyclic GMP, and thus their cognate signaling pathways, PDEs present intriguing targets for pharmacotherapies to combat alcohol use disorders. As activation of cAMP/cGMP-dependent signaling cascades can dampen alcohol intake, PDE inhibitors may provide a novel target for reducing excessive alcohol consumption, as has been proposed for PDE4 and PDE10A. This review highlights preclinical literature demonstrating the involvement of cyclic nucleotide-dependent signaling in neuronal and behavioral responses to alcohol, as well as detailing the capacity of various PDE inhibitors to modulate alcohol intake. Together these data provide a framework for evaluating the potential utility of PDE inhibitors as novel treatments for alcohol use disorders.
Insights
Cyclic nucleotide phosphodiesterases (PDEs) show promise for treating alcohol use disorders. PDE inhibitors may offer novel therapeutic targets to reduce excessive alcohol consumption and improve sobriety.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Alcohol use disorders (AUDs) are complex, relapsing conditions with limited treatment efficacy.
- Current treatments for AUDs do not fully address underlying causes, necessitating novel therapeutic strategies.
- Cyclic nucleotide phosphodiesterases (PDEs) are emerging as key regulators of alcohol consumption.
Purpose of the Study:
- To review preclinical evidence on the role of cyclic nucleotide signaling in alcohol responses.
- To evaluate the potential of phosphodiesterase (PDE) inhibitors as novel pharmacotherapies for AUDs.
Main Methods:
- Literature review of preclinical studies on cyclic nucleotide signaling and alcohol intake.
- Analysis of research on the effects of various PDE inhibitors on alcohol consumption.
- Examination of the involvement of cyclic nucleotide-dependent signaling in neuronal and behavioral responses to alcohol.
Main Results:
- Cyclic nucleotide-dependent signaling pathways are implicated in neuronal and behavioral responses to alcohol.
- Inhibitors of specific PDEs, such as PDE4 and PDE10A, have shown potential in preclinical models to reduce alcohol intake.
- Activation of cAMP/cGMP signaling cascades can attenuate alcohol consumption.
Conclusions:
- Phosphodiesterase (PDE) inhibitors represent a promising novel therapeutic avenue for alcohol use disorders.
- Targeting PDEs could offer a new strategy for reducing excessive alcohol consumption and aiding sobriety.
- Further research into PDE inhibitors may lead to improved pharmacological treatments for AUDs.
